The objective of this proposal is to assess the impact of upper body obesity (UBO) on carbohydrate and lipid metabolism in black as compared to white women. We have found that whereas UBO in white women is associated with insulin resistance with respect to in vivo glucose disposal and to in vitro adipocyte metabolism, these effects of body fat distribution were not apparent in black women. This presents an opportunity to investigate the mechanisms underlying the association between body fat distribution and health. In all our studies, we will match obese women for percent body fat, so that any metabolic differences found will be a function of fat distribution, not a function of total body fat. In the first experiment, the regulation of lipolysis in relation to body fat distribution will be studied in vivo and in vitro. Systemic lipolysis will be determined basally, and in response to insulin and to adrenergic agents. Plasma FTA and glycerol turnover, basal and posthormone hepatic glucose production, total body glucose uptake, net glucose and lipid oxidation and storage will be measured. In the same individuals, adipose tissue will be taken for measurement of basal lipolysis and of lipolysis inhibited by insulin and other agents, or stimulated by adrenergic agonists. We will relate differences in the sensitivity to lipolytic and antilipolytic agents in vitro to in vivo changes in systemic lipolysis. In the second experiment, we will investigate lipolytic activity in omental as compared to abdominal adipose tissue in UBO and lower body obese (LBO) women. In the third experiment, we will determine whether diminishing FFA flux will improve the impaired glucose oxidation and decrease the elevated lipid oxidation in both UBO and LBO women compared to leans. In the fourth experiment, we will investigate whether differences between UBO and LBO women in insulin sensitivity as measured by euglycemic insulin clamps are associated with differences in muscle fiber type and function. A major aim of each experiment is to document any differences between black and white women. From our studies to date, we expect that body fat distribution will have little impact on metabolism in black women but will have a detrimental effect on white women. These studies will be significant in differentiating in vivo and in vitro lipolytic response, nutrient uptake and disposal, and muscle morphology in relation to insulin resistance in UBO and LBO women and also will define any differences between white and black women that could translate to a differing health risk. This will clarify appropriate target groups for preventive or therapeutic intervention.